Solid particles comprising decellularized cardiac tissue extracellular matrix and methods for making and using the same

Abstract

The present disclosure relates generally to solid particles comprising decellularized cardiac tissue extracellular matrix and, more particularly, to solid particles comprising decellularized cardiac tissue extracellular matrix for use in biomolecule delivery, treatment of cardiac diseases or cardiac conditions, and methods of generating the solid particles.

1 . A solid particle comprising decellularized cardiac tissue extracellular matrix. 
     
     
         2 . The solid particle of  claim 1  being a microparticle. 
     
     
         3 . The solid particle of  claim 2  having a diameter of about 1 μm to about 100 μm. 
     
     
         4 . The solid particle of  claim 3  having a diameter of about 20 μm. 
     
     
         5 . The solid particle of  claim 1  being spherical. 
     
     
         6 . The solid particle of  claim 1  wherein the cardiac tissue is human or porcine. 
     
     
         7 . The solid particle of  claim 1  wherein 100% of the particle is decellularized cardiac tissue extracellular matrix. 
     
     
         8 . The solid particle of  claim 1  not being a liquid, hydrogel, or sol-gel ex vivo. 
     
     
         9 . The solid particle of  claim 1  having an elastic modulus of about 1.5 kPa to about 6.5 kPa. 
     
     
         10 . The solid particle of  claim 9  having an elastic modulus greater than about 2.5 kPa, about 3 kPa, about 3.5 kPa, about 4 kPa, about 4.5 kPa, about 5 kPa, about 5.5 kPa, about 6 kPa, about 6.5 kPa, or greater than about 2.5 kPa but less than about 6.5 kPa. 
     
     
         11 . The solid particle  claim 10  having an elastic modulus of about 4.5 kPa. 
     
     
         12 . The solid particle of  claim 1 , when exposed to or immersed in an aqueous environment, swell up to about 50-90% as compared to dECM particles or a hydrogel in a non-aqueous environment. 
     
     
         13 . The solid particle of  claim 12 , when exposed to or immersed in an aqueous environment, swell up to about 70% as compared to dECM particles or a hydrogel in a non-aqueous environment. 
     
     
         14 . The solid particle of  claim 1  being resistant to complete enzymatic degradation about 1.5 times, about 2 times, about 2.5 times, about 3 times, about 3.5 times, about 4 times, about 4.5 times, about 5 times, about 5.5 times, about 6 times, about 6.5 times, about 7 times, about 7.5 times, about 8 times, about 8.5 times, about 9 times, about 9.5 times, about 10 times, about 10.5 times, or about 11 times greater than a time for complete enzymatic degradation of a hydrogel or hydrogel precursor. 
     
     
         15 . The solid particle of  claim 14  being resistant to complete enzymatic degradation for about 24 hours. 
     
     
         16 . The solid particle of  claim 1  wherein the solid particle, in a physiological environment, releases one or more biomolecules at a controlled release rate over a period of time. 
     
     
         17 . The solid particle of  claim 16  wherein the period of time is about 24 hours, about 24-28 hours, about 28-32 hours, about 32-36 hours, about 36-40 hours, about 40-44 hours, or about 44-48 hours. 
     
     
         18 . The solid particle of  claim 17  wherein the period of time is about 24 hours. 
     
     
         19 . The solid particle of  claim 1  wherein the solid particle, in a physiological environment, releases one or more biomolecules at a controlled release rate of about 0.5 ppm/hour to about 4 ppm/hour, or about 0.5-1 ppm/hour, or about 1-1.5 ppm/hour, or about 1.5-2 ppm/hour (e.g., 2 ppm/hour), or about 2-2.5 ppm/hour, or about 2.5-3 ppm/hour, or about 3-3.5 ppm/hour, or about 3.5-4 ppm/hour, or about 4-4.5 ppm/hour, or about 4.5-5 ppm/hour. 
     
     
         20 . The solid particle of  claim 19  wherein the solid particle, in a physiological environment, releases one or more biomolecules at a controlled release rate of about 2 ppm/hour. 
     
     
         21 . The solid particle of  claim 1  wherein the solid particle, in a physiological environment, releases one or more biomolecules at a controlled release rate of about 35 ppm over 24 hours to about 45 ppm over 24 hours, or about 35-36 ppm over 24 hours, or about 36-37 ppm over 24 hours, or about 37-38 ppm over 24 hours (e.g., about 38 ppm over 24 hours), or about 38-39 ppm over 24 hours, or about 39-40 ppm over 24 hours, or about 40-41 ppm over 24 hours, or about 41-42 ppm over 24 hours, or about 42-43 ppm over 24 hours, or about 43-44 ppm over 24 hours, or about 44-45 ppm over 24 hours. 
     
     
         22 . The solid particle of  claim 21  wherein the solid particle, in a physiological environment, releases one or more biomolecules at a controlled release rate of about 38 ppm over 24 hours. 
     
     
         23 . The solid particle of  claim 1  wherein no more than about 20-50% of total protein is released from the solid particle within about 20-50 hour(s) following contact of the solid particle with a physiological environment. 
     
     
         24 . The solid particle of  claim 23  wherein no more than about 20%, no more than about 25%, no more than about 30%, no more than about 35%, no more than about 40% (e.g., no more than about 37%), no more than about 45%, or no more than about 50% of total protein is released from the solid particle within about 20 hours, about 25 hours, about 30 hours, about 35 hours, about 40 hours, about 45 hours, or about 50 hours (e.g., about 48 hours) following contact of the solid particle with a physiological environment. 
     
     
         25 . The solid particle of  claim 1  wherein no more than about 37% of total protein is released from the solid particle within about 48 hours following contact of the solid particle with a physiological environment. 
     
     
         26 . A solid particle comprising decellularized cardiac tissue extracellular matrix and at least one biomolecule that is chemically conjugated to the extracellular matrix. 
     
     
         27 . The solid particle of  claim 26  wherein the at least one biomolecule is a non-native biomolecule. 
     
     
         28 . The solid particle of  claim 27  wherein the biomolecule is a macromolecule or a small molecule. 
     
     
         29 . The solid particle of  claim 27  wherein the macromolecule is a macromolecule-loaded polymer. 
     
     
         30 . The solid particle of  claim 27  wherein the macromolecule or small molecule is one of a drug or a drug-loaded nanoparticle. 
     
     
         31 . The solid particle of  claim 26  wherein at least one surface of the solid particle is functionalized with one or more chemical and/or biological moieties. 
     
     
         32 . The solid particle of  claim 1  being formed by electrospraying. 
     
     
         33 . The solid particle of  claim 1  being formed by use of a microfluidic chip. 
     
     
         34 . A composition comprising the solid particle of  claim 1  and a second component. 
     
     
         35 . A pharmaceutical composition comprising the solid particle of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         36 . A patch comprising a biodegradable bioscaffold seeded with a plurality of the solid particles of  claim 1 . 
     
     
         37 . A solid particle consisting of decellularized cardiac tissue extracellular matrix. 
     
     
         38 . A solid particle consisting of decellularized cardiac tissue extracellular matrix and at least one biomolecule chemically conjugated to the extracellular matrix. 
     
     
         39 . A method of treating a cardiac disease or cardiac condition in a subject, comprising administering to the subject a therapeutically effective amount of the solid particles of  claim 1 , thereby treating the cardiac disease or cardiac condition. 
     
     
         40 . The method of  claim 39  wherein the subject has experienced a myocardial infarction prior to administration of the plurality of solid particles. 
     
     
         41 . The method of  claim 39  wherein, following administration of the plurality of solid particles, one or more of the following effects occurs in the subject: (1) preservation of cardiac function; (2) reduction in fibrosis and fibroblast activation; (3) stimulation of cardiomyocyte cell cycle activity; (4) angiogenesis in cardiac tissue; and (5) protection against ventricular wall remodeling. 
     
     
         42 . The method of  claim 39  wherein the plurality of solid particles is administered prior to, simultaneous with, or following treatment with a ventricular unloading modality.